Early diagnosis of bladder cancer by photoacoustic imaging of tumor-targeted gold nanorods

Elisa, Alchera, Matteo, Monieri, Mirko, Maturi, Irene, Locatelli, Erica, Locatelli, Silvia, Tortorella, Angelina, Sacci, Angelo, Corti, Manuela, Nebuloni, Roberta, Luciano, Filippo, Pederzoli, Francesco, Montorsi, Andrea, Salonia, Sandra, Meyer, Jithin, Jose, Pierangela, Giustetto, Mauro Comes, Franchina, Flavio, Curnis, Massimo, Alfano

Photoacoustics |

Detection and removal of bladder cancer lesions at an early stage is crucial for preventing tumor relapse and progression. This study aimed to develop a new technological platform for the visualization of small and flat urothelial lesions of high-grade bladder carcinoma in situ (CIS). We found that the integrin α5β1, overexpressed in bladder cancer cell lines, murine orthotopic bladder cancer and human bladder CIS, can be exploited as a receptor for targeted delivery of GNRs functionalized with the cyclic CphgisoDGRG peptide (Iso4). The GNRs@Chit-Iso4 was stable in urine and selectively recognized α5β1 positive neoplastic urothelium, while low frequency ultrasound-assisted shaking of intravesically instilled GNRs@Chit-Iso4 allowed the distribution of nanoparticles across the entire volume of the bladder. Photoacoustic imaging of GNRs@Chit-Iso4 bound to tumor cells allowed for the detection of neoplastic lesions smaller than 0.5 mm that were undetectable by ultrasound imaging and bioluminescence.